A new structurally atypical bradykinin-potentiating peptide isolated from Crotalus durissus cascavella venom (South American rattlesnake)
Venom glands of some snakes synthesize bradykinin-potentiating peptides (BPP's) which increase bradykinin-induced hypotensive effect and decrease angiotensin I vasopressor effect by angiotensin-converting enzyme (ACE) inhibition. The present study shows a new BPP (BPP-Cdc) isolated from Crotalu...
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| Published in: | Toxicon (Oxford) Vol. 90; pp. 36 - 44 |
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| Main Authors: | , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
Elsevier Ltd
01-11-2014
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Venom glands of some snakes synthesize bradykinin-potentiating peptides (BPP's) which increase bradykinin-induced hypotensive effect and decrease angiotensin I vasopressor effect by angiotensin-converting enzyme (ACE) inhibition. The present study shows a new BPP (BPP-Cdc) isolated from Crotalus durissus cascavella venom: Pro-Asn-Leu-Pro-Asn-Tyr-Leu-Gly-Ile-Pro-Pro. Although BPP-Cdc presents the classical sequence IPP in the C-terminus, it has a completely atypical N-terminal sequence, which shows very low homology with all other BPPs isolated to date. The pharmacological effects of BPP-Cdc were compared to BBP9a from Bothrops jararaca and captopril. BPP-Cdc (1 μM) significantly increased BK-induced contractions (BK; 1 μM) on the guinea pig ileum by 267.8% and decreased angiotensin I-induced contractions (AngI; 10 nM) by 62.4% and these effects were not significantly different from those of BPP9a (1 μM) or captopril (200 nM). Experiments with 4-week hypertensive 2K-1C rats show that the vasopressor effect of AngI (10 ng) was decreased by 50 μg BPP-Cdc (69.7%), and this result was similar to that obtained with 50 μg BPP9a (69.8%). However, the action duration of BPP-Cdc (60 min) was 2 times greater than that of BPP-9a (30 min). On the other hand, the hypotensive effect of BK (250 ng) was significantly increased by 176.6% after BPP-Cdc (50 μg) administration, value 2.5 times greater than that obtained with BPP9a administered at the same doses (71.4%). In addition, the duration of the action of BPP-Cdc (120 min) was also at least 4 times greater than that of BPP-9a (30 min). Taken together, these results suggest that BPP-Cdc presents more selective action on arterial blood system than BPP9a. Besides the inhibition of ACE, it may present other mechanisms of action yet to be elucidated.
•A new bradykinin-potentiating peptide (BPP) was isolated from Crotalus durissus cascavella venom.•The new BPP (BPP-Cdc) has a completely atypical N-terminal sequence: PNLPNYLGIPP.•BPP-Cdc shows very low homology with those all the other BPPs isolated to date.•The hypotensive effect of BPP-Cdc to BK was more potent than that of BPP-9a.•Other ACE-independent mechanisms of BPP-Cdc are suggested. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0041-0101 1879-3150 |
| DOI: | 10.1016/j.toxicon.2014.07.011 |